1. Field of the Invention
The invention relates to the field of psoriasis.
2. Background Art
Psoriasis, affecting about 2% of the population, is one of the most common human skin disorders that affect skin and joints. It is characterized by complex alterations of various cell types. This includes epidermal hyperproliferation and altered differentiation, as well as angiogenesis and dilation of dermal blood vessels (Schön, 1999; Lebwohl, 2003). In addition, a mixed leukocytic infiltrate is seen. It is composed of activated T lymphocytes, neutrophiles within the dermis and epidermal microabscesses, lining macrophages, and an increased number of dermal mast cells. Cytokines including tumor necrosis factor-α (TNF-α), and interleukin-1 (IL-1), interferon-γ (INF-γ), IL-6, IL-8, vascular endothelial growth factor (VEGF) and transforming growth factor-α (TGF-α) are thought to mediate the psoriatic tissue alterations (Schön, 1999).
For decades the ongoing controversy is whether psoriasis results from primary abnormalities in the epidermis or is immunologically based (Nickoloff et al., 2000). Although evidence is accumulating that it has an immunological basis others interpret psoriasis as a genetically determined, abnormal epithelial response pattern to infection and/or physicochemical skin insults.
It has become clear that psoriatic skin is a hotbed of epidermal growth factors and inflammatory mediators. Supportive evidence of a key role for such mediators comes from patients who respond to immunsuppressive, anti-inflammatory, and antiproliferative therapies such as cyclosporine, methotrexate, tacrolimus, corticosteroids, and ultraviolet-light-activated psoralen. However, extensive efforts aimed at transgenically delivered inflammatory mediators or keratinocyte growth factors to the skin have not completely reproduced the psoriatic phenotype (Xia et al., 2003), which has thus far only been faithfully modeled in animals by transplanting psoriatic skin onto mice with severe combined immunodeficiency disease (SCID). So far no reported mouse model for psoriasis mimics all characteristics seen in psoriasis in humans, including psoriatic arthritis which is present in up to 40% of psoriasis patients.
Since there is no naturally occurring animal skin disease mirroring both phenotype and immunopathogenesis of psoriasis, research into the pathogenesis of this common skin disorder has been severely hampered.
Consequently, there is a need for an efficient and significant animal model for the study of psoriasis and for testing drug candidates effective in the treatment of this disorder.